Hyperphenylalaninemia(HPA), an autosomal recessive disease, is the most common inborn error of amino acid metabolism, caused by the deficiency of phenylalanine hydroxylase(PAH) or tetrahydrobiopterin(BH4) which induced by mutations of genes. The accumulation of the clinical database and genetic information will enhance the development of novel personalized medicine and to provide more accurate and timely diagnostic and therapeutic approaches for HPA. This paper summarizes the correlations between HPA metabolism and PAH, BH4, pathogenic genes and their distributions in HPA, as well as the phenotypes and genotypes of HPA, so as to provide reference for personalized medicine for HPA.

Congenital heart disease (CHD) is a type of birth defects due to the abnormal development of heart and blood vessels during embryonic stage. Studies indicate that the etiology of CHD is complicated. Genetic and epigenetic mechanisms including chromosomal abnormalities, gene mutations, nucleic acid modifications, non-coding RNAs may play important roles in CHD. At present, genetic mechanisms such as chromosome abnormality and gene mutation have been widely used in the diagnosis and treatment of clinical diseases. However, the application of genetic and epigenetic modification in diagnosis and treatment of CHD still need further research. This paper reviews the relationship between chromosomal abnormality, gene mutation, copy number variation, epigenetic modification and the occurrence of CHD, which may provide a basis for further exploring the early diagnosis and individualized therapy of CHD.

Congenital esophageal atresia is one of the serious birth defects. Identifying the etiology and mechanism of esophageal development can provide clues for the effective prevention and treatment of congenital esophageal atresia. Recent studies have shown that a variety of transcription factors and signaling pathways (including Wnt signaling pathway, bone morphogenetic protein signaling pathway, SHH signaling pathway, vascular endothelial growth factor signaling pathway) are involved in esophageal proliferation, differentiation and other processes, promoting the normal development of esophagus. Understanding the regulatory mechanisms during the normal development of esophagus can give reference for the prevention and treatment of congenital esophageal atresia. This article reviews the research progress on related transcription factors and signaling pathways in esophageal development.

Objective: To compare the efficacy of percutaneous atrial septal defect (ASD) closure guided by transesophageal echocardiography (TEE) or guided by fluoroscopy in pediatric patients. Methods: Medical records of patients who underwent percutaneous ASD closure in the Children's Hospital, Zhejiang University School of Medicine from January 2017 to March 2018 were reviewed. There were 120 patients whose procedures were guided by TEE (TEE group), and 125 patients who had their procedures guided by fluoroscopy (fluoroscopy group). The performance of surgery, efficacy and postoperative complications were compared between two groups. Results: Percutaneous ASD closure was successful in all patients. The operation time was shorter in the TEE group than that in fluoroscopy group[(20±14) min vs. (29±11) min, t=-7.939, P < 0.05]. The size of the defect was larger in the TEE group than that of fluoroscopy group[(11±4) mm vs. (9±4) mm, t=2.512, P < 0.05], but there was no significant difference in the sizes of occluder and occluder sheath between two groups (all P>0.05). No residual shunt, occluder shedding or displacement, severe arrhythmia or pericardial effusion were observed in either group. The incidence rates of fever, cough and diarrhea were not statistically different between two groups (all P>0.05). Conclusion: There was no significant difference in the outcome of percutaneous ASD closure guided by TEE or by fluoroscopy, but the procedure guided by TEE may reduce the operation time and can evaluate the size of ASD more accurately without involving radiation exposure, contrast agents use and large digital subtraction equipment.

Objective: To evaluate the application of echocardiography in diagnosis of pediatric pulmonary artery sling. Methods: Twenty-five children diagnosed as pulmonary artery sling in the Children's Hospital, Zhejiang University School of Medicine from July 2012 to August 2017, and 50 healthy children(control group) were enrolled in the study. Echocardiography was performed in all subjects. The origins of the left pulmonary artery(LPA) and right pulmonary artery(RPA) were observed; the internal diameters of LPA, RPA and main pulmonary artery(MPA) were measured; and the ratios of LPA/MPA and RPA/MPA were calculated. The value of RPA/MPA and LPA/MPA in diagnosing pulmonary artery sling was evaluated by ROC curve. Results: Echocardiography showed that the internal diameters of RPA were increased in all patients; while the LPA and blood flow signals in common pulmonary arterial bifurcation were not found in 24 cases, in whom the MPA was directly extended to the RPA, and the LPA was from the massive RPA. The ultrasound of one special case showed that there was no distinct bifurcation of MPA; the MPA walked to the right and then to the left with no change in the internal diameter. There were significant differences in RPA/MPA(0.50±0.05 vs. 0.71±0.15, t=7.06, P < 0.01) and LPA/MPA(0.52±0.05 vs. 0.39±0.09, t=6.94, P < 0.01) between controls and the patients. ROC curve analysis showed that the AUC of RPA/MPA and LPA/MPA in diagnosis of pulmonary artery sling were 0.90 and 0.89, respectively. When taking 0.60 as the cutoff value, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of RPA/MPA in diagnosis of pulmonary artery sling were 79%, 100%, 100%, 91% and 93%, respectively. When taking 0.43 as the cutoff value, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of LPA/MPA in diagnosis of pulmonary artery sling were 71%, 96%, 89%, 87% and 88%, respectively. Conclusions: Echocardiography can effectively diagnose pediatric pulmonary artery sling. The RPA/MPA ratio of 0.60 and the LPA/MPA ratio of 0.43 can be used as cutoff values for diagnosis.

Objective: To summarize experience in the treatment of complex congenital intestinal atresia in children, so as to investigate the key points and effect of the operation. Methods: Medical notes of 49 children with complex intestinal atresia treated between January 2012 and January 2018 were reviewed. The information of age, sex, age at operation, full-term or premature, birth weight, clinical manifestation, auxiliary examination, preliminary diagnosis, treatment process, discharge diagnosis, pathological results and prognosis of patients were analyzed. Results: All patients underwent surgical treatment, including 42 cases with laparotomy (85.7%) and 7 with laparoscopic surgery (14.3%); 1 case undergoing laparoscopic surgery was converted to laparotomy due to meconium peritonitis. The mean operation time was (147±43) min (70-270 min); the mean fasting time after surgery was (8±3) d (4-16 d); the mean parenteral nutrition time was (12±6) d (3-30 d). Eleven cases were discharged against medical after operation and lost to follow-up. Among rest 38 children, 1 child (2.6%) received intestinal resection and ostomy five days after operation due to gastrointestinal perforation; 1 child (2.6%) received conservative treatment one month later due to adhered intestinal obstruction and left hospital with cure; 1 child (2.6%) received enterodialysis and ileostomy eight days after operation due to anastomotic leak, and received the operation for the closure of fistula after three months; 4 children had complications including fluid and electrolyte disorders, anemia, hypoproteinemia and so on, and recovered after conservative treatments. Postoperative follow-up showed that 1 child with duodenal atresia had lower body weight at 6 month after operation, but the body weight returned to normal when the child was one year old; 1 child with preterm labor of 32 weeks was treated with enteral nutrition, and gradually restored the normal diet after 6 months. Growth retardation was not observed in other children. Conclusion: With active treatment and reservation of normal bowel tube as much as possible during the operation, the prognosis of children with complex intestinal atresia is usually favorable.

Objective: To evaluate the efficacy and safety of transumbilical single-site laparoscopic surgery for congenital duodenal obstruction (CDO) in neonates. Methods: A retrospective analysis of clinical data of 15 patients with CDO undergoing transumbilical single-site laparoscopic treatment during November 2017 and January 2018 (single-site group), and 20 patients with CDO undergoing conventional three-hole laparoscopic treatment during August 2017 and October 2017 (three-hole group) was performed. All patients were from the Children's Hospital, Zhejiang University School of Medicine. The operation time, time of initial feeding, time of adequate feeding, length of hospital stay after operation and postoperative complications were compared between two groups. Results: The operations were completed in all patients. No patient converted to laparotomy, and no massive hemorrhage was observed during operation. The operation time of single-site group was (90±10) min for patients with duodenal diamond-shaped anastomosis and (81±15) min for patients with Ladd operation, while those of three-hole group were (85±9) min and (72±11) min, respectively. Postoperative initial feeding time of single-site group was (5.0±1.0) d, and that of the three-hole group was (4.8±0.8) d. The adequate feeding time was (9.0±1.2) d in the single-site group, and (9.3±0.8) d in the three-hole group. The length of hospital stay after operation was (11.2±2.5) d in the single-site group, and (11.5±2.8) d in the three-hole group. There was no significant difference in operation time, postoperative initial feeding time, adequate feeding time and length of hospital stay after operation between two groups (all P>0.05). Conclusion: Transumbilical single-site laparoscopic surgery for CDO in neonates is safe and effective, and the postoperative abdominal scar is more hidden.

Objective: To compare the efficacy of thoracoscopic surgery versus thoracotomy in repairing esophageal atresia type Ⅲ with tracheoesophageal fistula (EA/TEF) in neonates. Methods: A retrospective analysis was conducted in 97 neonates who underwent EA/TEF repair between January 2012 and December 2017 in the Affiliated Children's Hospital of Nanjing Medical University, including 75 patients receiving thoracotomy and 22 patients receiving thoracoscopic surgery. The perioperative data and the incidence of early postoperative complications were compared between two groups. Results: The operations were completed in all patients. One child (4.5%) in thoracoscopic surgery group was converted to thoracotomy with modified Livaditis procedure due to the long distance of two blind ends (>4 cm) and thinner distal end. The operation time was longer in thoracoscopic surgery group[(143±48) min vs. (120±40) min, P < 0.05], but the postoperative ventilation time was shorter[(55±22) h vs. (65±19) h, P < 0.05] and the first oral feeding was earlier in thoracoscopic surgery group[(3.2±1.1) d vs (3.9±1.3) d, P < 0.05]. No statistical difference was observed in the ratio of red blood cell transfusion, length of hospital stay and drainage tube indwelling time between two groups (all P>0.05). The incidence of lung complications in thoracotomy group was higher than that in thoracoscopic surgery group (20.0% vs. 9.1%, P < 0.01), while there were no significant differences in the incidence of other postoperative complications between two groups. There was no death in thoracoscopic surgery group, while 2 patients died in thoracotomy group. Conclusion: Thoracoscopic repair is a preferred surgical procedure for EA/TEF in neonates.

Objective: To evaluate the feasibility of endoscopic lobectomy for pulmonary sequestration in children. Methods: Clinical data of 47 children with pulmonary sequestration treated with endoscopic lobectomy from April 2015 to November 2017 were reviewed. According to the operation date, 19 children received operation from April 2015 to December 2016 were early group, and 23 children received operation from January 2017 to November 2017 were late group (5 children with lesions inside diaphragm were excluded). The operation time, intraoperative blood loss, retention time of drainage tube, length of hospital stay and incidence of complications were compared between two groups. Results: Among 47 children, endoscopic lobectomy was successfully completed in 45 children, and the rest 2 children were converted to thoracotomy. No death was observed. The operation time in late group was shorter than that in the early group (P < 0.05), and the intraoperative blood loss of the late group was less than that of early group (P < 0.05); while there were no significant differences in retention time of drainage tube and length of hospital stay between two groups (both P>0.05). Postoperative complications occurred in 14 children, including 4 cases of pneumothorax, 8 cases of pleural effusion, 1 case of pulmonary infection, and 1 case of diaphragmatic hernia. The incidence rates of postoperative complications in late group and early group were 17.4% (4/23) and 42.1% (8/19), and the difference was not statistically significant(P>0.05). During the follow-up (2-26 months), no relapse and thoracic collapes were observed, and CT examination found that the remaining lungs were well compensated in all children. Conclusion: The endoscopic lobectomy is effective and safe with less trauma and bleeding, which is recommended for treatment of pulmonary sequestration in children.

Objective: To analyze complications after laparoscopic Ladd operation for intestinal malrotation, related causes and possible solutions. Methods: Clinical data of 81 neonates who underwent laparoscopic Ladd operations for intestinal malrotation in the Children's Hospital, Zhejiang University School of Medicine between January 2015 and January 2018 were reviewed. The abdominal complications and findings during operation and reoperation were analyzed. Results: Operations were successfully completed in all patients, and there was no patient converted to open surgery. The annular pancreas in 6 cases and duodenal diaphragm in 4 cases were confirmed during the operation. The recurrent volvulus developed in 3 patients (3.7%), of whom 2 cases were confirmed to have midgut necrosis during open surgery 1 week and 3 months after laparoscopic Ladd operation, and both finally died; 1 case was corrected by second laparoscopic operation. Cecal perforation occurred in 1 patient (1.2%), which was caused by intensive high frequency coagulation of the appendiceal stump. One patient (1.2%) developed chylous ascites and improved after conservative treatment. Adhesive small bowel obstruction was observed in 3 cases (3.7%), and all relieved after conservative treatment. Conclusion: Laparoscopic Ladd operation for intestinal malrotation in neonates was effective, and the incidence of abdominal complications may be minimized by experienced skills and strict perioperative management.

Objective: To review the application of thoracoscopic repair for treatment of congenital diaphragmatic hernia in neonates, so as to improve the cure rate. Methods: Clinical data of 47 neonates with congenital diaphragmatic hernia receiving thoracoscopic repair from June 2012 to June 2017 were reviewed. The admission age, gestational age, birth weight, timing of diagnosis, hernia location, clinical manifestation, surgical timing, surgical method, operation time, postoperative mechanical ventilation time of patients were analyzed. Results: There were 42 cases of left diaphragmatic hernia and 5 cases of right diaphragmatic hernia. Thirteen cases were diagnosed prenatally. Primary diaphragmatic repair was successfully accomplished under thoracoscope in 45 neonates without perioperative complications, while 2 patients were converted to open surgery. The average operation time was (63±13) min (42-150 min), the average blood loss was (3.0±1.7) mL (1.0-9.0 mL), and the average postoperative mechanical ventilation time was (3.9±1.4) d (2.0-11.0 d). Two patients died and the treatment was withdrawn in 3 patients with an overall cure rate of 89.4% (42/47). Conclusion: Thoracoscopic repair is effective and can be used as first-choice treatment of diaphragmatic hernia in neonates.

Objective: To evaluate the application of cameral-type three-dimensional (3D) scan in the assessment of funnel chest. Methods: Eighty children with funnel chest were collected from the Children's Hospital, Zhejiang University School of Medicine during June 2016 and December 2017. All patients underwent routine CT scan. In the same selected mediastinal window, the lowest point of the depression to the front of the spine was the anteroposterior diameter (A₁), and the maximum left to right diameter was B₁ (which was perpendicular to A₁). The ratio B₁/A₁ was calculated to get CT Haller index (CT-HI). In the same period, the chest wall scan was performed by EinScan-Pro 3D scanner, and the image was analyzed by GeoMedic image software. On the plane of the most concave point of the sternum, the distance from the lowest point of the skin to the back skin was the anteroposterior diameter (A₂), the maximum plane diameter was measured on the same plane (B₂), and the ratio B₂/A₂ was the 3D-Haller index (3D-HI). Pearson correlation analysis was used to analyze the consistency of the two measurements. Kappa test was used to analyze the consistency of surgical indication based on cutoff value of CT-HI and 3D-HI. Results: All children were able to cooperate with CT and 3D chest wall surface scan. The mean value of CT-HI was 3.82±0.96, and that of 3D-HI was 1.82±0.23. Pearson correlation analysis showed that the correlation coefficient between CT-HI and 3D-HI was 0.823 (P < 0.01). When CT-HI > 3.2 and 3D-HI > 1.7 were set as cutoff values for indication of operation, the sensitivity and specificity of 3D-HI were 90.48% and 100.0%, respectively. 3D-HI was well consistent with CT-HI in surgical indication (Kappa=0.801). Conclusions: 3D scan can be used to assess the funnel chest in children, and 3D-HI>1.7 can be used as the cutoff value for surgical indication.

Objective: To identify the commonly used Chinese traditional herb Rostellularia procumbens (L.) Nees. Methods: The appearance, morphological features and microscopic characteristics were adopted to identify Rostellularia procumbens (L.) Nees. Results: Rostellularia procumbens (L.) Nees is an annual herb with typical spike, but without involucre bracts under inflorescence. The corolla appears 2 labiate lips and 2 stamens. The capsularfruit consists of 4 seeds. The stems of the herbs are six-ribbed and cylindrical with the lavender node.The oblong leaves with full margin are wrinkled and bent.The herbs are tasteless. The pollen grains is long-oval shaped with 2-colposate, and the pollen exine presents with concentrated echinate sculpture. Stomata is diacytic type with non-glandular hairs, and mostly consists of 3-5 cells. Glandular scales are more common and composed of 4 cells with intumescent and oblate head. There are numerous long-elliptical or clavate calcium carbonate crystals (cystolith) in the stems and leaves, with papillary protruding. Conclusion: The appearance, morphological features and microscopic characteristics can be used for the quality identification of Rostellularia procumbens (L.) Nees.

Objective: To identify pine needles from different plant origins by microscopic and molecular approaches. Methods: The characteristics of pine needles of Pinus massoniana Lamb., Pinus thunbergii Parl. and Pinus armandii Franch. were investigated via plant morphology and microscopic characteristics. ITS2 and rbcL were analyzed with PCR amplification and bi-directional sequencing. MEGA 6.0 was used to calculate the intra-and inter-specific Kimura-2-Parameter (K2P) distances, and the phylogenetic tree was constructed by using the neighbor-joining (NJ) method. Results: There were significant differences in the number and length of pine needles, number of vascular bundles, distribution of stomatal lines, number and distribution of resin channels among three kinds of pine needles. The lengths of ITS2 sequences of Pinus massoniana Lamb., Pinus thunbergii Parl. and Pinus armandii Franch. were 470, 469 and 470 bp, respectively. The lengths of rbcL sequences in three kinds of pine needles were 553 bp. The intraspecific variation rates of ITS2 sequences in Pinus massoniana Lamb., Pinus thunbergii Parl. and Pinus armandii Franch. were 0%, 0.2%, and 2.8%, respectively; and the intraspecific variation rates of rbcL sequences were 0%, 2.4%, and 1.1%, respectively. There was no significant barcoding gap in intraspecific and interspecific genetic distances of ITS2 sequences. The intraspecific and interspecific distances of rbcL sequences were clearly separated in the barcoding gap test. The NJ tree based on rbcL showed that the three pine needles clustered into three separate groups, indicating that rbcL DNA marker could distinguish the Pinus massoniana Lamb., Pinus thunbergii Parl., Pinus armandii Franch. and its close relative species. Conclusions: The three types of pine needles can be distinguished accurately and rapidly by microscopic and molecular identification. The study provides methodology and experimental basis for the quality evaluation and classification of pine needles.

Olfactory adaptation is an important physiological function of animals, which can protect their own neurons from overstimulation, and be better to deal with all kinds of stimuli in the surrounding environment. In this article, we discuss the neuronal basis of olfactory adaptation in Caenorhabditis elegans. Up to now, several intracellular regulatory factors have been discovered to be associated with olfactory adaptation in Caenorhabditis elegans, including cyclic guanosine monophosphate (cGMP) signaling in the olfactory neurons AWC, OSM-9 in transient receptor potential vanilloid (TRPV) channel, arrestin ARR-1, diglyceride (DAG) pathway in G protein signaling pathways, etc. However, the neural circuits of the olfactory adaptation remains largely unknown. This paper reviews molecular and cell biological mechanism of olfactory adaptation in Caenorhabditis elegans, so as to provide reference for studies on olfactory sensation in advanced animals.

Total knee arthroplasty is an effective method for the treatment of end-stage knee osteoarthrosis, which can effectively relieve joint pain and reconstruct the integrity of the joint. Whether the posterior cruciate ligament should be preserved during surgery or not, which is still in dispute. In recent years, posterior cruciate-retaining and substituting total knee prostheses are both applied in clinical practice. Both domestic and international studies have shown that there are no significant difference in patient satisfaction, knee flexion, survival rate of the prosthesis and the main clinical manifestations between two prostheses. However, posterior cruciate-retaining total knee prosthesis is more consistent with the normal physiology and biomechanics of the human body. The gait is more balanced and proprioceptive when walking up and down the stairs, but when the joints are buckling, the femur is abnormal to move back to the tibia, resulting in abnormal motion. While posterior cruciate-substituting total knee prosthesis can correct severe deformity of the knee, and keep better balance between flexion and extension of the knee joint, but there is a potential complication of patellar clunk syndrome. Therefore, under the same conditions, the younger patients may prefer to chose posterior cruciate-retaining total knee prosthesis, while elder patients may prefer to chose posterior cruciate-substituting total knee prosthesis. This paper reviews the function of posterior cruciate ligament, as well as the advantages and disadvantages of two prostheses, so as to provide some references for clinic.

Exosome is a specific subset of vesicles from intracellular origin vesicles containing varies of microRNAs, mRNAs, proteins and lipids. It has been demonstrated that contents of exosomes could be altered due to different physiological and pathological stress, which could be used as clinical biomarker to reveal the disease state. In addition, according to previous studies, exosomes could exert protective roles for cardiovascular diseases such as atherosclerosis, myocardial infarction and ischemia/reperfusion injury, etc. The aim of this review is to summarize current research progress on exosomes, related implications in diagnosis and treatment of cardiovascular diseases and corresponding mechanisms.